The musculoskeletal system includes a variety of dense and soft connective tissues, including cartilage, bone, tendon, ligament, spinal intervertebral discs, and muscle. Musculoskeletal tissues differentiate embryonically from mesenchymal precursor cells.
An example of musculoskeletal tissue is cartilage. Three types of cartilage exist in mammals: hyaline cartilage, fibrocartilage, and elastic cartilage. Hyaline cartilage includes the articular cartilage of the joints, the cartilages of the trachea, bronchi, and larynx, and the nasal cartilages. Fibrocartilage is found in the intervertebral disc, tendinous and ligamentous insertions, menisci, the symphysis pubus, and insertions of joint capsules. Elastic cartilage is found in the pinna of the ears, in the epiglottis, and in the arytenoid cartilages of the larynx.
Musculoskeletal tissues play a variety of functional roles. For example, the spinal intervertebral discs serve as the shock absorbers of the axial body and also allow for considerable flexibility and motion. Each disc is composed of a peripheral, ligament-like annulus fibrosus and a central nucleus pulposus (NP). The NP contains chondrocyte-like cells embedded in a matrix of proteoglycan and type II collagen that is highly hydrophilic and allows the tissue to swell to resist compressive forces. The NP environment is one of high pressure, low pH, and low oxygen tension.
Musculoskeletal diseases are a major health concern. As an example, disc degeneration is a common feature among the aging population and is the underlying cause of various spinal disorders and disabilities. Disc degeneration is also believed to be the predominant cause of low back pain, which is the second most frequent reason for patients to visit their physicians and affects approximately 80% of the population at some point in their lives. When patients fail to respond to conservative care, a spinal fusion is typically performed even though it leads to immobility of the treated segments and predisposes adjacent discs to accelerated degeneration. A significant number of these patients do not benefit from fusion and require further treatments.
Another adverse musculoskeletal condition is arthritis, which affects millions of people in the United States alone. Although metallic joint replacements offer relief for some individuals with advanced disease, these devices have limited durability and are not suitable for young or highly active patients. Focal cartilage defects represent an early manifestation of arthritis. Sports injuries and trauma-induced focal cartilage defects are typically treated with microfracture (a procedure where small holes are drilled thru cartilage and into the underlying bone to stimulate healing), which has short-term benefits but also fails after 5-10 years. Despite its limitations, microfracture remains the gold standard for treatment. Recently, therapies that utilize autologous chondrocytes have been pursued; however, the use of a patient's own articular cartilage cells is critically limited by insufficient cell availability, donor site morbidity, cell heterogeneity, and inconsistent regenerative capacity.
There is a need in the art for compositions and methods of producing various musculoskeletal tissues.
Literature
    Richardson et al. (2006) Stem Cells 24:707; Yamamoto et al. (2004) Spine 29:1508; Le Visage et al. (2006) Spine 31:2036; Vadalá et al. (2008) Spine 33:870; WO 2003/068149; U.S. Pat. Nos. 6,355,239, 5,908,784, 5,486,359, 6,835,377.